Ligand preorganization in metal ion complexation: Molecular mechanics/dynamics, kinetics, and laser-excited luminescence studies of trivalent lanthanide complex formation with macrocyclic ligands TETA and DOTA

The molecular mechanics and dynamics calculations, kinetics, and laser-exci ted luminescence studies were carried out for trivalent lanthanide (Ln(3+)) complexes of macrocyclic polyaminopolycarboxylate ligands TETA and DOTA (w here TETA is 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid an d DOTA is 1,4,7,10-tetraazacy-clododecane-1,4,7,10-tetraacetic acid) to fur ther understand the observed thermodynamic, kinetic, and structural propert ies and to examine how ligand preorganization affects metal ion complexatio n. Excitation spectroscopy (emission monitored at 614.0 nm) of the F-7(0) - D-5(0)- transition of Eu3+ was used to study the aqueous properties of the Eu3+-TETA system. A stopped-flow spectrophotometric method was used to stu dy the formation kinetics of the aqueous Ce3+-TETA/DOTA systems in the pH r ange 6.1-6.7. Molecular mechanics calculation results are consistent with t he proposed mechanism of Ln(DOTA)- formation, i.e., formation of a. carboxy late O-bonded precursor, followed by metal ion moving into the preformed ma crocyclic cavity. For Ln(TETA)- formation, at least two carboxylate O-bonde d intermediates have been predicted and Ln(3+) ion assisted reorganization of the TETA ligand is present. The calculated bond distances and overall st ructures of Ln(DOTA)- and Ln(TETA)were in agreement with the single-crystal and solution NMR structural data. The origin of thr difference in thermody namic stability of Ln(DOTA)- and Ln(TETA)- complexes and the corresponding formation intermediates is mainly due to the differences in water-occupancy energy (i.e., whether there is an apical coordinated water molecule), the ligand strain energy, and the cation-ligand interaction energy. Kinetic stu dies revealed that the formation rates of the Ce(TETA)- complex are smaller at lower pH and temperature but become greater at higher pH and temperatur e, as compared to those of the Ce(DOTA)- complex. This is attributed to the lanthanide ion and both mono- and di-hydroxide ion assisted TETA conformat ional reorganization and higher kinetic activation parameters. The presence of a di-hydroxide ion assisted intermediate rearrangement pathway could ma ke the Ce(TETA)- complex formation rate faster at higher pH, and the higher activation barrier makes Cr(TETA)complex formation rate slower at lower pH , as compared to those of the Ce(DOTA)- complex.